Exhaustive High-Yield University Study Notes: Neurology

Core Principles of Stroke: Risk Factors and Pathophysiology

• Primary Risk Factors: In the context of the USMLE, the two most critical risk factors for cerebral infarction (stroke) are hypertension (HTN) and atrial fibrillation (AF).
• Mechanism of Hypertension in Stroke: Persistent hypertension creates a strong systolic impulse that pounds against the carotid arteries. This mechanical stress causes endothelial damage, fostering the development of atherosclerotic plaques (carotid stenosis). These plaques or associated thrombi can eventually dislodge ("launch off") and embolize to the brain or eye.
• Mechanism of Atrial Fibrillation in Stroke: Atrial fibrillation causes blood turbulence and stasis within the heart, particularly in the left atrium. This leads to the formation of a left atrial (LA) mural thrombus, which can embolize to the cerebral circulation.
• Population Statistics vs. Clinical Scenarios: While HTN is statistically the most common risk factor for stroke across the general population, if a patient presents with both AF and HTN in a vignette, the USMLE considers AF the more important/likely risk factor for the current event.
• Preventative Priorities: Controlling blood pressure is considered more effective for reducing stroke risk than smoking cessation.
• Summary of Embolic Sources: Most strokes occur either due to atheromatous plaques from carotid stenosis (driven by HTN) or an LA mural thrombus (driven by AF).

Stroke Syndromes and Vascular Territories

• Anterior Cerebral Artery (ACA): Stroke results in motor and sensory abnormalities localized to the contralateral leg.
• Middle Cerebral Artery (MCA):     * Results in motor and sensory abnormalities of the contralateral arm and face.     * Dominant MCA Stroke (usually Left): Can manifest as Wernicke or Broca aphasia.     * Non-dominant MCA Stroke (usually Right): Can cause hemispatial neglect (e.g., the patient is unable to draw a clockface or ignores the left side of their environment).
• Posterior Cerebral Artery (PCA):     * Results in contralateral homonymous hemianopsia with macular sparing.     * Can cause prosopagnosia (the inability to recognize familiar faces).
• Lateral Medullary Syndrome (Wallenberg Syndrome):     * Typically caused by an infarct of the Posterior Inferior Cerebellar Artery (PICA) or the vertebral artery.     * Key clinical tetrad: Dysphagia (difficulty swallowing) + Ipsilateral Horner syndrome (miosis, partial ptosis, anhidrosis).     * Mnemonic: "PICAchew" (Pikachu) refers to the dysphagia caused by a PICA stroke.
• Medial Medullary Syndrome:     * Caused by an infarct of the anterior spinal artery.     * Classic finding: Ipsilateral tongue deviation.     * Can also cause contralateral paralysis and loss of proprioception.
• Lateral Pontine Syndrome:     * Caused by an infarct of the Anterior Inferior Cerebellar Artery (AICA).     * Clinical marker: Ipsilateral Bell's palsy (facial nerve involvement).     * Mnemonic: "FACIAL" contains AICA backwards.
• Weber Syndrome:     * Occurs in the midbrain.     * Manifests as ipsilateral Cranial Nerve III (CN III) palsy ("down and out" eye) and contralateral spastic hemiparesis (weakness).
• Locked-in Syndrome:     * Caused by a basilar artery stroke or central pontine myelinolysis.     * Characterized by the inability to move the entire body except for the eyes.
• Gerstmann Syndrome:     * Caused by a stroke of the angular gyrus of the parietal lobe.     * Clinical tetrad: 1) Agraphia (inability to write); 2) Acalculia (inability to perform math); 3) Finger agnosia (inability to identify fingers); 4) Left-right dissociation.
• Hemiballismus:     * Caused by a stroke involving the subthalamic nucleus.     * Presents as "ballistic," violent flailing of the contralateral arm and leg.

Lacunar Infarcts and Small Vessel Disease

• Lipohyalinosis: This is the mechanism by which chronic hypertension causes microatheroma formation in the small, penetrating lenticulostriate arteries deep within the brain.
• Lacunar Infarct Pathogenesis: Ischemia in these small vessels leads to tissue necrosis and subsequent reabsorption, leaving behind small cavities called lacunae.
• Clinical Presentation: Unlike cortical strokes, lacunar infarcts typically do not present with aphasia, neglect, or visual field loss. Common syndromes include pure motor hemiparesis, pure sensory stroke, or ataxic hemiparesis.
• Charcot-Bouchard Microaneurysms: These are tiny aneurysms ($< 1\,mm$) forming in the lenticulostriate arteries. Their rupture causes intraparenchymal (intracerebral) hemorrhagic strokes.

Microscopic and Cellular Responses to Injury

• Liquefactive Necrosis: This is the specific type of necrosis seen following injury to the nervous system tissue.
• "Red Neurons": The acute histologic change seen in ischemic CNS infarction, characterized by strong eosinophilic (pink) staining on H&E. This differs from myocardial infarction, where no changes are seen immediately.
• Microglia: These are the resident macrophages of the CNS; they are responsible for phagocytosing necrotic tissue.
• Astrocytes: These glial cells proliferate following injury to form a glial scar (gliosis). They are the cells responsible for scar formation in the CNS.
• Wallerian Degeneration: Refers to the degradation of the axon and myelin sheath distal to a site of injury.     * Regrowth speed: Maximum of $1\,mm/day$.     * PNS vs. CNS: Regeneration occurs in the Peripheral Nervous System (via Schwann cells) but not effectively in the Central Nervous System (because oligodendrocytes do not regenerate myelin effectively).     * Optic Nerve Distinction: The optic nerve (CN II) is myelinated by oligodendrocytes (extension of CNS), meaning injury leads to permanent blindness. Other cranial nerves are PNS (myelinated by Schwann cells) and have higher regenerative potential.

Vertebrobasilar Insufficiency and Vascular Dissections

• Subclavian Steal Syndrome:     * Occurs when there is stenosis of the proximal subclavian artery before the vertebral artery branch point.     * Creates lower pressure in the vertebral artery, causing a reversal of flow (backflow) to the arm.     * Key Finding: Difference in blood pressure between the two arms and dizziness.     * Management: CT or MR angiography. If BP is different between arms, USMLE often points to aortic dissection, but if dizziness is present, consider subclavian steal.
• Vertebral Artery Stenosis: Presents like subclavian steal (dizziness) but lacks the blood pressure discrepancy between arms. Caused by atherosclerosis.
• Vertebral Artery Dissection:     * A false lumen leads to stasis, clot formation, and eventual embolization/stroke.     * Buzzy trigger: Recent visit to a chiropractor or neck manipulation.     * Management: USMLE requires Heparin for posterior stroke due to vertebral dissection.

Types of Aphasia

• Wernicke (Fluent):     * Speech is fluent but nonsensical ("word salad").     * Comprehension is impaired; repetition is impaired.     * Location: Temporal lobe (Left MCA infarct).
• Broca (Non-fluent):     * Speech is "telegraphic" and slow; comprehension is intact, but the patient is frustrated.     * Repetition is impaired.     * Location: Frontal lobe (Left MCA infarct).
• Conductive:     * Only repetition is impaired.     * Cause: Damage to the arcuate fasciculus (connects Broca and Wernicke).
• Global: Combination of Broca, Wernicke, and Conductive (repetition impaired).
• Transcortical Sensory: Similar to Wernicke, but repetition is intact.
• Transcortical Motor: Similar to Broca, but repetition is intact.

Stroke Management and Procedures

• Initial Diagnostic Step: Non-contrast CT of the head. This is essential to distinguish between ischemic and hemorrhagic stroke. Blood appears hyperdense (bright white).
• Ischemic Stroke Treatment:     * tPA: Administered if symptom onset is within $4.5\,hours$. The window begins from the time the patient was last confirmed normal.     * Aspirin: Given if the $4.5\text{-hour}$ window has passed.     * BP Management: BP must be lowered to $< 185/110\,mmHg$ before tPA can be given. Once below this, BP is controlled cautiously to maintain perfusion to the ischemic penumbra.
• Hemorrhagic Stroke Treatment:     * Contraindication: Never give tPA.     * BP Management: Rapidly reduce systolic BP to $< 140\,mmHg$ using labetalol, nicardipine, or hydralazine.     * Anticoagulation Reversal: Give Fresh Frozen Plasma (FFP) if the patient is on warfarin.

Sodium Correction and Cerebral Edema

• Cerebral Edema: Caused by correcting hypernatremia too quickly using hypotonic saline.
• Central Pontine Myelinolysis (CPM):     * Caused by correcting hyponatremia too quickly using hypertonic saline.     * Described as "osmotic demyelination."     * Results in Locked-in Syndrome.

Intracranial Pressure and Delirium States

• Hypercalcemic Crisis: Severe hypercalcemia (from malignancy or Primary Hyperparathyroidism) causes delirium. Treatment is normal saline followed by bisphosphonates (e.g., pamidronate).
• Pseudotumor Cerebri (Idiopathic Intracranial Hypertension):     * Increased ICP with no structural cause.     * Signs: Papilledema, absent venous pulsations on fundoscopy.     * Associations: Obesity, Oral Contraceptive Pills (OCPs), hypervitaminosis-A, isotretinoin, and danazol.
• Reye Syndrome: Cerebral edema and hepatotoxicity caused by giving aspirin to children during a viral infection. Due to impaired beta-oxidation.
• Diffuse Axonal Injury (DAI): Caused by deceleration injuries (MVAs). MRI shows scattered white (hyperintense) lesions. Requires relearning basic tasks.

Spinal Cord Tracts and Functions

• Spinothalamic Tract:     * Function: Pain and temperature from the contralateral body.     * Decussation: Occurs at the level of the spinal cord (anterior white commissure).
• Corticospinal Tract:     * Function: Motor function for the ipsilateral body below the lesion.     * Decussation: Medulla (pyramidal decussation).
• Dorsal Columns:     * Function: Vibration and proprioception from the ipsilateral body.     * Clinical Marker: (+) Romberg test if disrupted (patient falls when eyes are closed).
• Upper vs. Lower Motor Neuron Signs:     * UMN (Cortex to Anterior Horn): Hyperreflexia, hypertonia, clonus, (+) Babinski sign.     * LMN (Anterior Horn to Muscle): Hyporeflexia, hypotonia/flaccidity, fasciculations, atrophy.

Clinical Spinal Syndromes

• Tabes Dorsalis: Destruction of dorsal columns by neurosyphilis. Results in bilateral loss of vibration/proprioception, ataxia, and (+) Romberg. Myelin stain shows white (demyelinated) dorsal columns.
• Syringomyelia: Cyst (syrinx) in the anterior white commissure. Causes bilateral loss of pain and temperature in a "cape-like" distribution. May eventually involve the corticospinal tract.
• Brown-Sequard Syndrome (Hemisection):     * Ipsilateral loss of vibration/proprioception (Dorsal Column).     * Ipsilateral loss of motor function (Corticospinal).     * Contralateral loss of pain/temp (Spinothalamic).     * Triggers: Viral infection, SLE, or transverse myelitis.
• Central Cord Syndrome: Weakness in the upper limbs is significantly greater than in the lower limbs. Classically occurs after hyperextension "whiplash" injuries in the elderly.
• Anterior Cord Syndrome: Preservation of dorsal columns (vibration/proprioception) but loss of motor function and pain/temperature. Seen in anterior spinal artery disease.

Brachial Plexus and Birth Injuries

• Erb-Duchenne Palsy: Upper plexus injury ($C5-C6$). Arm is adducted, pronated, and wrist is flexed ("waiter's tip").
• Klumpke Palsy: Lower plexus injury ($C8-T1$). Results in a "claw hand."
• Spina Bifida:     * Meningocele: Herniation of meninges.     * Meningomyelocele: Herniation of meninges and spinal cord.     * Timing: Occurs between $3-4\,weeks$ gestation.     * Risk: Folic acid deficiency or use of valproic acid, phenytoin, or carbamazepine.     * Markers: Increased AFP and acetylcholinesterase in CSF/amniotic fluid.

Degenerative Spinal Conditions

• Cervical Spondylosis: Degenerative changes in the cervical spine in patients $> 50$. Due to degeneration of the pars interarticularis.
• Atlantoaxial Subluxation: Increased mobility between $C1$ (atlas) and $C2$ (axis). Highly yield in patients with Rheumatoid Arthritis (RA). Requires neck imaging before intubation for surgery.
• Lumbar Spinal Stenosis:     * Pain worse when walking down a hill (leaning forward relieves it).     * Can cause "neurogenic claudication" where pulses are normal but walking causes pain.
• Cervical Foraminal Stenosis: Stenosis of the foramen where the nerve exits. Example: $C7-T1$ stenosis causes sensory loss in the little finger and hand muscle weakness.
• Spondylolisthesis: Characterized by a palpable "step-off" between vertebrae.
• Disc Herniation (Radiculopathy):     * Pathology: Nucleus pulposus herniates through a tear in the annulus fibrosis.     * Trigger: Heavy lifting or bending.     * Management: NSAIDs and light exercise. Bed rest and imaging (X-ray/MRI) are wrong for simple radiculopathy unless motor deficits exist.     * $L4$ Radiculopathy: Loss of patellar reflex, weakened knee extension.     * $L5$ Radiculopathy: Loss of dorsiflexion (cannot walk on heels).     * $S1$ Radiculopathy: Loss of Achilles reflex, weakened plantar flexion (cannot walk on toes).

Peripheral Nerve Injuries (Lower Limb)

• Common Peroneal (Fibular) Nerve: Loss of both eversion and dorsiflexion.
• Superficial Peroneal Nerve: Loss of eversion only; sensation loss at lower lateral leg/dorsum of foot.
• Deep Peroneal Nerve: Loss of dorsiflexion only ("high-steppage gait"); sensation loss between 1st and 2nd toes.
• Tibial Nerve: Loss of plantar flexion (cannot stand on tippy-toes) and inversion.
• Obturator Nerve: Inability to adduct the hip; sensation loss at the medial thigh.
• Femoral Nerve: Buckling of the knee; inability to extend the knee.
• Saphenous Nerve: Pure sensory branch of femoral; sensation loss at the medial calf.
• Sural Nerve: Sensation loss at the lower lateral calf. Preferred for nerve grafts because it is purely sensory.
• Superior Gluteal Nerve: Innervates gluteus medius/minimus. Damage causes Trendelenburg gait (pelvis falls on opposite side).
• Inferior Gluteal Nerve: Innervates gluteus maximus. Damage causes inability to climb stairs or stand from a chair.

Peripheral Nerve Injuries (Upper Limb)

• Axillary Nerve ($C5-C6$): Flattened deltoid; loss of sensation over lateral upper arm. Caused by surgical neck humerus fractures.
• Median Nerve:     * Innervates lateral 3.5 fingers and thenar pad.     * Carpal Tunnel Syndrome: Compression at the wrist. Management: Wrist splint, then triamcinolone injection. Surgery is generally considered wrong for USMLE unless severe.     * Injury site: Supracondylar humerus fracture.
• Ulnar Nerve:     * Innervates medial 1.5 fingers.     * Froment Sign: Inability to pinch paper between thumb and index without bending the index.     * Guyon Canal Syndrome: Compression at the wrist (hook of hamate fracture; cyclists).     * Cubital Tunnel Syndrome: Compression at the elbow. Management: Overnight elbow splint.
• Radial Nerve:     * Innervates "BEST": Brachioradialis, Extensors (wrist/fingers), Supinator, Triceps.     * Injury: Midshaft humerus fracture leads to wrist drop and pronated forearm.
• Musculocutaneous Nerve: Innervates biceps; sensory loss at lateral forearm.

Hydrocephalus Variants

• Communicating: CSF flows freely but reabsorption is failed (Arachnoid granulations). Common after meningitis.
• Non-communicating (Obstructive): Blockage within ventricles. Examples: Aqueductal stenosis (between 3rd/4th ventricles), Colloid cysts.
• Normal Pressure Hydrocephalus (NPH): "Wet, wobbly, wacky" (incontinence, ataxia, cognitive decline). Caused by corona radiata impingement. Incontinence mechanism: failure to inhibit voiding reflex.
• Hydrocephalus ex-vacuo: Apparent enlargement of ventricles due to brain matter loss (Alzheimer/Schizophrenia).

Dementia and Cognitive Decline

• Alzheimer Disease:     * Beta-amyloid plaques and neurofibrillary tangles (tau).     * Down Syndrome link: APP gene on Chromosome 21.     * Treatment: Donepezil (Cholinesterase inhibitor) and Memantine (NMDA antagonist).
• Frontotemporal Dementia (Pick Disease): Personality change, apathy, and disinhibition. Pick bodies (round tau inclusions).
• Lewy Body Dementia: Dementia + Visual hallucinations + Parkinsonism. Alpha-synuclein deposition throughout the brain.
• Vascular Dementia: Step-wise decline (though USMLE focuses on motor/sensory focal deficits). Due to mini-strokes.
• Pseudodementia: Depression presenting as cognitive decline. MMSE improves with prompting.
• Subacute Combined Degeneration: B12 deficiency. Affects corticospinal tracts, dorsal columns, and spinocerebellar tracts.

Movement Disorders

• Parkinson Disease:     * Loss of dopamine in substantia nigra pars compacta.     * Features: Resting "pill-rolling" tremor, bradykinesia, cogwheel rigidity.     * Treatment: Carbidopa-Levodopa. High doses can cause psychosis (treatment: decrease dose).
• Restless Leg Syndrome (RLS): Primarily caused by iron deficiency. Check ferritin. Treat with pramipexole/ropinirole.
• Wilson Disease: Parkinsonism in a young patient. Copper accumulation in basal ganglia.
• Progressive Supranuclear Palsy: Parkinsonism + Axial dystonia.
• Huntington Disease: Autosomal Dominant CAG repeat on Chromosome 4. Degeneration of caudate nuclei. Chorea and anticipation.

Demyelinating Disorders and Autoimmune Pathology

• Multiple Sclerosis (MS):     * T-cell attack on oligodendrocytes/CNS myelin.     * Relapsing-remitting. Optic neuritis and Internuclear Ophthalmoplegia (INO) are classic.     * Findings: Urge incontinence, IgG oligoclonal bands in CSF, white matter plaques on MRI.     * Treatment: IV methylprednisolone for flares; Beta-interferon to prevent recurrence.
• Guillain-Barre Syndrome (GBS):     * Attack on Schwann cells/PNS myelin.     * Ascending paralysis, loss of DTRs.     * CSF: Albuminocytologic dissociation (high protein, normal cells).     * Treatment: IVIG or plasmapheresis. Steroids are wrong.
• Myasthenia Gravis: Antibodies against postsynaptic ACh receptors. Ptosis/diplopia worsens with use. Associated with Thymoma.
• Lambert-Eaton Syndrome: Antibodies against presynaptic voltage-gated Calcium channels. Weakness improves with use. Associated with Small Cell Lung Cancer.

Headache and Vertigo Management

• Trigeminal Neuralgia: Lancinating pain triggered by minor stimuli. Treat with Carbamazepine.
• Cluster Headache: Male, wakes from sleep, 11/10 pain with rhinorrhea/lacrimation. Acute treatment: 100% Oxygen. Prophylaxis: Verapamil.
• Migraine: Unilateral, throbbing. Prophylaxis: Propranolol. Abortive: Triptans (5HT agonists).
• Temporal Arteritis: Painful headache in patients $> 50$. High ESR. Give IV steroids before biopsy to prevent blindness.
• Benign Paroxysmal Positional Vertigo (BPPV): Brief vertigo episodes from dislodged otoliths (calcium carbonate stones). Dx: Dix-Hallpike. Tx: Epley maneuver.

Seizures and Epilepsy

• Focal-onset Aware (Simple Partial): No loss of consciousness (LoC).
• Focal-onset Impaired Awareness (Complex Partial): LoC present. Often involves staring.
• Tonic-Clonic (Grand Mal): Generalized. Postictal confusion and tongue biting are markers.
• Status Epilepticus: Seizure $> 5\,minutes$. Order of Tx: Benzo (Lorazepam) $\rightarrow$ Phenytoin $\rightarrow$ Phenobarbital.
• Absence Seizure: Child staring off, symmetric $3\text{-Hz}$ spike-and-wave. Treat with Ethosuximide.
• Febrile Seizure: Occurs in kids $6\,months$ to $5\,years$. No risk if brief; increased risk of epilepsy if $> 10\,minutes$.

Neuro-Infectious Diseases

• Meningitis:     * Neonates: GBS ($Strep. agalactiae$), Listeria, E. coli.     * Adults: $S. pneumoniae$, $N. meningitidis$.     * Bacterial CSF: Low glucose, high protein, high neutrophils.
• Herpes Encephalitis: Temporal lobe hemorrhage leads to RBCs in CSF. Treatment: IV Acyclovir.
• Toxoplasmosis: Ring-enhancing lesions in HIV. Prophylaxis: TMP-SMX (CD4 $< 100$). Treatment: Sulfadiazine + Pyrimethamine.
• Primary CNS Lymphoma: Single ring-enhancing lesion in HIV if on TMP-SMX.
• Neurocysticercosis: Pork tapeworm ($T. solium$). Cystic brain lesions. Treat with Albendazole.

Intracranial Hemorrhage Types

• Epidural Hematoma: Rupture of Middle Meningeal Artery. Lens-shaped, lucid interval. High ICP treatment: intubation + hyperventilation.
• Subdural Hematoma: Rupture of bridging veins. Crescent-shaped. Risk in elderly/alcoholics.
• Subarachnoid Hemorrhage (SAH): Rupture of Berry aneurysm (AcoM/PcoM). "Worst headache of life." Nimodipine prevents vasospasm.
• Intracerebral Hemorrhage: Rupture of Charcot-Bouchard aneurysms (Lenticulostriate) or Amyloid Angiopathy (Alzheimer).

Questions & Miscellaneous High-Yield Discussion

• Carotid Sinus Hypersensitivity: Patient loses consciousness while shaving; tilt-table test is normal.
• Metoclopramide: Non-antipsychotic drug that can cause Tardive Dyskinesia.
• Bupropion: Antidepressant that lowers seizure threshold.
• Anterograde Amnesia: Thiamine (B1) administration in alcoholics helps reduce this risk most significantly.
• Parenchymal Findings: "Mousy" odor = PKU; "Crumpled tissue paper" macrophages = Gaucher; "Cherry red spot" + no HSM = Tay-Sachs; "Cherry red spot" + HSM = Niemann-Pick.
• Waardenburg Syndrome: White forelock + deafness = failure of neural crest migration.
• Double Cortex Syndrome: Failure of radial migration of neurons.
• Rett Syndrome: Hand-wringing in female infants.
• Brain Tumors: Pilocytic astrocytoma (Rosenthal fibers, kid), Medulloblastoma (vermis/ataxia, kid), Glioblastoma (Butterfly, adult), Meningioma (adult), Schwannoma (CN VIII/NF2).